WEDNESDAY MORNING, APRIL 24, 1968

8:30 A.M. Scientific Session: THORACIC SURGERY FORUM

Ballrooms 1 and 2

31. Homologous Aortic Valve Transplantation: Alterations in Viable and Non-Viable Valves

Hitoshi Mohri,* Dennis D. Reichenbach,* Robert W. Barnes,*

and K. Alvin Merendino, Seattle, Wash.

Our experiments with 40 dogs demonstrated low antigenicity and satisfactory, prolonged function of the homologous aortic valve without evidence of rejection. Surviving donor cells of viable grafts and absence of host substitution of nonviable valves up to 6 months post-transplantation were noted. Most institutions are now advocating the use of fresh viable grafts although their ultimate fate is still unknown. Recent studies, however, show that fresh valves undergo a histologic alteration with the passing of time. One year after transplantation, viable grafts still demonstrated surviving donor cells although the percent of sex chromatin positive cells had decreased. Furthermore, specimens obtained one year and one specimen obtained 6 months postoperatively showed areas of segmental acellularity and thinning of the leaflet, although these valves were functioning satisfactorily. Non-viable grafts, on the other hand, demonstrated definite host substitution by one year, represented by a fibroblastic sheath over the cusp extending from the host and by fibroblastic cell invasion into the surface of the leaflet. No scarring or restricted movement of the leaflet was observed. The late fate of viable and non-viable valves is being evaluated in 17 remaining animals (8 viable and 9 non-viable grafts) up to 20 months post-transplantation. The pros and cons of each graft, including clinical specimens, will be discussed.

32. The Immunologic Response to Heterotopic Allovital Aortic Valve Transplants in Presensitized and Nonsensitized Recipients

Arthur E. Baue, William J. Donawick,* and William S. Blakemore,

Philadelphia, Pa.

Unrelated calves were prepared by donor-to-recipient and autologous skin grafts. After 9 day first-set rejection, recipients received donor buffy coat (6 x 10⁸ ells) in multiple intramuscular sites. The recipient's pulmonic valve was then replaced by the donor's aortic valve, priming the extracorporeal system with stored autologous blood. Ten animals survived, had 7 day second-set skin rejection, were sacrificed at 7-223 days and compared with heterotopic allovital valve transplants in nonsensitized calves. In a third group, allogeneic aortic and autologous pulmonic valve leaflets alone were implanted intramuscularly after prosthetic valve substitution. Biopsies of implants at 7-14 days demonstrated progressive sensitization, massive mononuclear cell and allogeneic leaflet destruction. In situ functioning valve transplants did not show this form of allograft rejection, even in presensitized recipients. Initial minimal mononuclear cell infiltration was not found after 40 days. All transplants persisted and many leaflets were thin, yascularized, transparent and functionally normal, with viable-appearing leaflet cells. A focal histiocytic and fibroblastic cell reaction progressed through the graft, suggesting tissue restructuring and replacement. Transplanted valves did not increase in size as the animals grew and were associated with large pressure gradients and calcification at the base in presensitized recipients.

33. Photographic Analysis of the Active and Passive Components of Cardiac Valvular Action

Richard T. Padula,* George S. M. Cowan,*

and Rudolph C. Camishion, Philadelphia, Pa.

Detailed observations of the motion of cardiac valves in a living, beating heart have not been made. The movements of valves seen in pulse duplicators are only passive. Thus, it is unlikely that they are the same as those produced when the annuli, cordae tendinae, and papillary muscles actively participate in valvular function. A system we have previously described before this Association has been improved to permit in vivo, intracardiac photography in dogs. Color motion pictures were obtained through a newly developed fiber-optical lens system illuminated by a mercury vapor lamp. Intracardiac pressures and aortic flow were simultaneously recorded. During cardiac asystole, photographs were again taken while the valves were activated by an external pump which duplicated intracardiac pressures and flow. In the beating heart, rotational closure of the aortic cusps, annular contraction with narrowing of the valvular orifices and contraction of the papillary muscles were observed. Movements of the mitral leaflets during diastole, which may cause the third heart sound were seen. All these findings were absent when the valves were activated by the external pump. Color motion pictures will be shown. The implications of this preparation for in vivo study of valvular prostheses will be presented.

34. Long-Term Observation of the Changes in Pulmonary Vascular Resistance after Autotransplantation of the Canine Lung

Charles R. H. Wildevuur,* H. Heemstra,* K. Tammeling,*

C. Hilvering,* H. Bouma,* F. Ten Hoor, and J. Kleine,*

Cleveland, Ohio

Sponsored by Donald B. Effler

Pulmonary hypertension is a major complication after autotransplantation of the lung in dogs. Structural defects of the anastomosis are mainly found to be the cause. However, pulmonary hypertension has also been reported in dogs without structural defects. In order to evaluate the cause of these cases, a study was undertaken to investigate the extent and the course of the high vascular resistance in the reimplanted lung. In a group of 29 dogs, 18 long-term survivals were examined by pneumoangio-graphy, bronchography, bronchospirometry, and occlusion of the contralateral pulmonary artery with a balloon-catheter. In nine dogs, no detectable structural defects were found. In this group, two dogs had a higher than normal increase in pulmonary artery pressure after occlusion with a balloon-catheter. One year after reimplantation, these nine dogs underwent contra-lateral pneumectomy. The increase in pressure after ligation of the contralateral pulmonary artery at this time now indicated a high vascular resistance in the reimplanted lungs of five dogs. Six dogs survived the contralateral pneumectomy. In the following study all of these dogs manifested a pulmonary hypertension. This study suggests that in the reimplanted lung of a dog, a slow and progressive increase of the vascular resistance takes place.

35. The Hemodynamic Effects of Serotonin in Pulmonary Embolism

George R. Daicoff, Florencio R. Chavez,* Aaron H. Anton,*

and Edward W. Swenson,* Gainesville, Fla.

The intravenous injection of serotonin (5 micrograms/kg. of body weight) in anesthetized dogs resulted in pulmonary arterial hypertension and intrapulmonary venous hypertension without a significant change in the left atrial pressure or pulmonary vein pressure measured just outside the pericardium. Premedication with the serotonin antagonist, methysergide (0.5 micrograms/kg. body weight) was capable of preventing the pulmonary arterial and venous hypertension of the subsequent administration of serotonin (5 micrograms/kg. body weight). Dogs given autologous clots (1 cc/kg. body weight) developed significant pulmonary arterial and intrapulmonary venous hypertension. The clots contained an average dose of 1 microgram endogenous serotonin/kg, body weight. These control dogs failed to survive an average dose of 1.5 cc clot/kg. Dogs premedicated with methysergide 0.5 micrograms/kg. developed a comparable degree of pulmonary hypertension with 1.75 cc of clot/kg, without intrapulmonary venous hypertension. These dogs tolerated three times the amount of clot given to control dogs and failed to develop intrapulmonary venous hypertension. The technique of pulmonary venous cannulation and pressure measurement will be described. The sustained intrapulmonary venous hypertension developed with pulmonary embolism as opposed to the transient effect with a single dose of serotonin will be discussed. The effect of methysergide administration after pulmonary embolism will be presented.

36. Experimental Hyperkinetic Pulmonary Hypertension: Tolerance After Biventricular Hypertrophy Produced by a Femoral Arteriovenous Fistula

Charles H. Dart, Jr.,* Oteen, N.C., Thomas Montgomery,* and

Richard M. Peters, Chapel Hill, N. C.

Attempts at production of significant hyperkinetic (high blood flow) pulmonary hypertension in dogs have been unsuccessful because the large shunts required lead to early pulmonary edema and death. Hyperkinetic pulmonary hypertension has been produced when shunt flow was confined to one or part of one lung. Unconditioned dogs all died within two weeks when a one centimeter dacron prosthetic graft was used as pulmonary artery - aortic shunt. When biventricular hypertrophy was produced with a 1.5 cm. long femoral arteriovenous fistula six to eight weeks prior to the insertion of the shunt, seven of nine dogs survived from one month to three and one half years. Electromagnetic probe measurements of shunt flow prior to closing the chest ranged from 1200 to 2000 cc/min. Indwelling catheters were inserted in the pulmonary artery, left atrium, and aorta for blood manometric and oxygen determinations. In the conditioned dogs mean and systolic pulmonary arterial pressure, pulmonary arterial oxygen saturations, and shunt calculations were consistent with hyperkinetic pulmonary hypertension. The systolic pulmonary arterial pressures ranged from 35 to 70. Creation of a simple peripheral A-V fistula conditions a dog so that high blood flow pulmonary hypertension can be produced.

37. Automatic Measurement of Tidal Volume in Postoperative Patients

F. John Lewis, and Vijai K. Moses,* Chicago, Ill.

Frequent measurement of at least some of the parameters of respiratory mechanics should help the surgeon in the early recognition of postoperative respiratory complications. To obtain this, we have developed and will describe a digital computer system which provides frequent and automatic measurement of respiratory rate, tidal volume, minute volume, and other parameters which may be derived from a continuous measurement of respiratory air flow. Air flow is estimated from transthoracic electrical impedance sensed by skin electrodes. Calibration is carried out by using the pneumotachygraph as a standard. From about 30 seconds of simultaneous impedance and pneumotachygraph signals, the computer program develops a calibration factor for the impedance signal. Following this, signals from the impedance skin electrodes alone provide the data upon which pattern identification and computation is carried out for a reporting of respiratory parameters every two or three minutes. The validity of the technique has been tested by statistical methods on the records of 15 patients. Implications of this and similar methods for obtaining maximum information with minimal disturbance to the patient through the use of engineering and computer technology will be discussed.

38. Assisted Circulation by Synchronous Pulsation of Extramural Pressures

H.S. Soroff,* U. Ruiz,* W.C. Birtwell,* M. Many,* F. Gordon,*

and R. A. Deterlino, Jr., Boston, Mass.

Assisted circulation has been carried out by introducing energy into the vascular system by synchronous pulsatile modification of external pressure on portions of the body. A system has been designed in which the lower extremities of the animal are enclosed in a double-walled seal which is in turn enclosed in a rigid housing. Water is introduced between the two walls of the seal and is subjected to synchronous pulsatile pressures. The PTM values are reduced by 15%,and the peak aortic diastolic pressure is elevated by 40%, while cardiac output is increased by 15%. The application of external cardiac assist combined with cardiac massage to animals in ventricular fibrillation for five minutes has resulted in an increase of aortic pressure and cerebral blood flow of 65% and 154% respectively as compared with external massage alone. With cardiac massage alone no successful resuscitations were achieved. The combined assist resulted in four out of five successful resuscitations. Studies in normal human volunteers show a 20% reduction in systolic pressure and a 50% increase in diastolic pressure. The results in patients in cardiogenic shock and cardiac arrest will be discussed.

39. Clinical Experience With Counterpulsation in Coronary Artery Disease

John Arthur Jacobey,* Denver, Colo.

Sponsored by William R. Waddell

Experimental studies demonstrate that counterpulsation can provide effective circulatory assistance by lowering systolic blood pressure, and it can improve myocardial perfusion by elevating diastolic or coronary perfusion pressure. Dilatation of dormant coronary collateral circulation by counterpulsation has been experimentally demonstrated using both in vivo and postmortem coronary arteriography. Metabolic studies have not successfully evaluated counterpulsation because its two separate effects make studies of arterioyenous differences inconclusive. If counterpulsation can improve coronary circulation by opening up dormant collateral channels, it should be beneficial in chronic coronary disease as well as acute. Six patients with severe three-vessel coronary disease have been studied with pre- and post-treatment selective coronary arteriography and standardized treadmill tests when indicated. At least twelve patients should be studied before this meeting. Pre- and post-treatment arteriograms demonstrate increased coronary circulation in five patients. Standardized post-treatment treadmill studies in three patients were normal in one with significant increase in exercise tolerance in two. Four returned to normal activity. Two patients are dead with extensive myocardial fibrosis from previous infarctions, emphasizing the need for earlier treatment. Technical aspects will be emphasized because standardization of this procedure is badly needed to clarify conflicting reports based on unstandardized experimental studies of counterpulsation.

40. An Automatic Implantable Intrathoracic Total and Partial Circulatory Support System

William R. Rassman,* Susumu Tanaka,* Randolph M. Ferlic,*

Minneapolis, Minn., and C. Walton Lillehei, New York, N.Y.

Circulatory support has been primarily approached by two methods: 1) Left heart bypass may benefit heart disease limited to the left side of the heart. However, if associated right heart disease or severe pulmonary vascular changes secondary to left sided lesions are present, success is unlikely with these support systems. 2) Counterpulsation, which has similar advantages and disadvantages, is said to augment coronary artery circulation. Previous investigations here revealed that there is an increase in external work with both systems. The limitations and univentricular nature of the above systems led to the development of implantable intrathoracic support system. A semi-rigid cylinder surrounds the heart and contains an inflatable bladder. Intermittent inflation of the bladder massages the heart. Cardiac output, blood pressure and rate can be partially or completely controlled synchronously. Total circulatory support of the fibrillating heart has been sustained for periods up to 17 hours with complete return of normal circulation after discontinuance of support. Significant pathologic alterations in the myocardium have not been demonstrated. Physiologic and biochemical measurements on metabolic work under normal and pathologically stressed circulatory workloads in synchronously supported hearts will be presented.

41. Alterations in Fibrinolytic and Coagulation Factors During Cardiopulmonary Bypass

John M. Porter,* and Donald Silver,* Durham, N.C.

Sponsored by David C. Sabiston, Jr.

This study was designed to evaluate the magnitude, rate, and duration of changes in fibrinolytic activity and coagulation factors during and after cardiopulmonary bypass. Methods: Blood samples were obtained pre-operatively, at 15 minute intervals during bypass, and at intervals post-operatively for 7 days from 25 patients. The samples were assayed for fibrinolytic activity, platelet counts, clotting times and prothrombin. Factors V and VII, and fibrinogen concentrations. Urokinase excretion was determined at similar intervals. Results: Fibrinolytic activator activity increased 350% (average) and returned to normal within 1 hour after bypass. Prothrombin, Factors V and VII concentrations, and platelet counts were reduced to 20-30% during bypass but returned to control levels within 4 hours after bypass. Fibrinogen was reduced to 30% during bypass. After bypass, fibrinogen increased to 200% of the control by Day 7. Clotting times were prolonged 25% for 4 hours. Urokinase excretion varied and appeared unrelated to circulating activator activity. Conclusion: Fibrinolytic activity increases at a tune related linear rate while on bypass and is accompanied by significant reduction of coagulation factors. The changes return to normal within 4 hours and remain normal except for a prolonged elevation of fibrinogen. Therapeutic aspects of these changes will be discussed.

42. Transthoracic Left Atrial Cannulation: A New Approach

G. C. Rastelli,* Jack L. Titus,* and Dwight G. McGoon,

Rochester, Minn.

The left atrium may be cannulated transthoracically and without fluoroscopy through a tubular graft positioned during the primary operation in those patients considered prone to develop progressive low cardiac output after cardiovascular surgery. One end of a Teflon graft 12 mm in diameter was sutured over the base of the unopen left atrial appendage in 12 dogs. The other end of the graft was led out of the chest through an intercostal space and buried under the skin. One hour to 30 days after operation a Silastic Pezzer-type cannula 6.3 mm in inside diameter, with the mushroom tip stretched over a stylet, was advanced through the exposed graft and positioned into the left atrial cavity after perforating the atrial wall. The graft was tightened over the cannula, the stylet was withdrawn, and left ventricular bypass at flow rates up to 3 liters/min was performed in six animals for 4 to 24 hours. The cannula was then withdrawn and the graft ligated. Seven dogs were allowed to recover. Morphologic observations up to 45 days after cannulation in the dog will be reported. Additional experience with left atrial cannulation in 10 human cadavers will be presented.

43. Superiority of Right Heart Systolic Pressure over Central Venous Pressure Monitoring in Preventing Overtransfusion

F. T. Thomas,* New York, N.Y.

Sponsored by Frank C. Spencer

Central venous (CV) pressure is not always a reliable guide in preventing overtransfusion in surgical patients. In search of a more reliable index of overtransfusion, experiments were performed in 13 dogs comparing CV pressure to left ventricular and end-diastolic (LVED), left atrial (LA), pulmonary artery systolic (PAS), pulmonary artery diastolic (PAD), right ventricular systolic (RVS) and right ventricular end-diastolic (RVED) pressures during hypervolemic transfusions of 1500-2000 ml. of blood given in 500 ml. increments every thirty minutes. The degree of physiological pulmonary edema was gauged by serial monitoring of the arterial PO₂ and the degree of anatomical edema by weighing the lungs at the conclusion of the experiment. With overtransfusions of greater than 1000 ml., the arterial PO₂ fell virtually in direct proportion to the amount of Overtransfusion, reaching values of 25 - 40 mm. Hg. with 2000 ml. of overtransfusion. LVED, LA, PAD, RVED, and CV pressures transiently rose 5-12 mm. above normal for 10-20 minutes following each 500 ml. of overtransfusion. However, these values then returned to normal despite worsening pulmonary edema. In contrast, RVS and PAS pressures remained elevated 10-25 mm. Hg. above normal for periods up to one hour after each 500 ml. of overtransfusion. Monitoring of serial arterial PO₂ values and serial PAS or RVS pressures during rapid transfusion provides the most sensitive safeguard against overtransfusion.

*By Invitation